Bone metabolic diseases are disorders of bone formation, bone resorption and deposition of bone minerals caused by disturbance of normal bone metabolism from congenital or acquired factors. Bone metabolic diseases include osteoporosis, vitamin D deficiency, vitamin C deficiency, renal osteodystrophy, etc. Among these bone metabolic diseases, osteoporosis is a common and frequent disease. Osteoporosis is a systematic and systemic bone disease characterized by brittleness increase of bone and high risk of fracture caused by bone loss, bone tissue microstructure destruction. As living standard of people continuously improves, life span of people prolongs and aging society comes, osteoporosis has become a common and frequent disease that seriously threatens health of the middle and old aged; particularly for menopause women, the balance of bone formation and bone resorption is disturbed by variation in estrogen level, resulting in massive bone loss, increase of bone resorption and/or descent of bone formation, causing osteoporosis, and even worse, osteoporotic fracture.
China is not only the country having the largest amount of population, but also the country having the largest amount of osteoporosis patients. Based on the fifth nationwide census, the male incidence of osteoporosis is 14.6% and the female incidence of osteoporosis is 61.8% in the old-aged above 60 years old, with an overall incidence of 6.97% and totally 88.26 million of middle and old aged threatened by occurrence of osteoporosis. To Mid 21 Century, China will come into the peak period of the aged society, the population above 60 constitutes 27% of the total population, reaching up to 400 million. As a result, the research and development on the drugs to prevent and treat osteoporosis have a great sense in improving the health of people and increasing life quality and also have a great social value.
Currently, the drugs used for treating osteoporosis mainly include four classes: one is bone resorption inhibitors such as a variety of diphosphonate compounds, Isopropyl isoflavones, calcitonin, estrogen and selective estrogen receptor modulator; one is bone formation-accelerating drugs such as fluoride, parathyroid hormone, insulin-like growth factor, protein synthetic hormone; one is ossification-accelerating drugs such as calcium, vitamin D and its derivatives; one is drugs for inhibiting the activity of osteoclast and enhancing bone formation such as strontium ranelate; and other classes such as traditional Chinese medicine.
Among the drugs for treating osteoporosis, diphosphonate drugs inhibiting bone resorption are the most commonly used. Diphosphonate drugs, i.e. pharmaceutically-acceptable salts, are synthetic analogue of natural pyrophosphate, having the basic structure shown in formula I:

As shown in formula I, R′, R″ lateral chains in diphosphonate molecular structure may affect its bone affinity. Typically, R′ is H, OH or halogen and the like groups, R′ has a smaller influence on the bone affinity of diphosphonate drugs; and the structure of R″ is a main factor that affects the bone affinity of diphosphonate drugs. Currently, based on different structures of R″, commercially available diphosphonate drugs generally include the following three classes: the first is that R″ is diphosphonate salt not comprising nitrogen, represented by Etidronate, clodronate, and clinically applied in the 70s last century; the second is that R″ structure comprises amino group, having a stronger ability of inhibiting bone resorption than the diphosphonate drugs without nitrogen, represented by Panidronate, alendronate. The third is that R″ is diphosphonate salt comprising nitrogen containing heterocycle, having an even stronger ability of inhibiting bone resorption and an easier clinical application, represented by Zoledronate which has a bone affinity over 10000 times stronger than Etidronate. Diphosphonate drugs comprising N (comprising —NH2 or comprising N heterocycle) or not comprising N both treat osteoporosis through inhibiting the activity of osteoclast and have a weak effect on osteoblast proliferation. Although commercially available diphosphonate drugs have a more and more stronger effect on inhibiting osteoclast but also increase the risk of fracture, and moreover it has not reported that diphosphonate drugs have effect on osteoblast proliferation.